Nucleic Acid Inhibitors Flashcards
Which are the Fuoroquinolones
Ciprofloxacin
Levofloxacin
Gemifloxacin
Monifloxacin
Fluoroquinolones are derived from
Nalidixic Acid which is the Quinolone Mother Substance
Spectrum/Uses of Ciprofloxacin
Narrow spectrum
Potent activity against Gram-negative aerobic organisms
Enterococci
Pseudomonas Aeruginosa
Haemophilus
Neisseria
Legionelle
Ciprofloxacin is used for
DOC for Typhoid fever
Cystitis
Meningococcal Prophylaxis
LRT Infections
What is Ciprofloxacin not used for
Gram +ive bacteria (Streptococci and Pnemococci)
Anaerobic bacteria
Gonorrhoea
Spectrum/Uses of Moxifloxacin, Gemifloxacin and Levofloxacin
Active against Gram +ive
LRTis
Acute sinusitis
Skin infections
Levofloxacin is used to treat
UTI
Soft tissue infections
M.Tuberculosis
Moxifloxacin is used to treat
M.Tuberculosis
When are Moxifloxacin, Gemifloxacin and Levofloxacin used to treat Respiratory infections
In cases of B-Lactam allergy
Spectrum/uses of Norfloxacin
Only used in UTIs
Wider spectrum
Structurally similar to Nalidixic acid
Spectrum/Uses of Nalidixic acid
Very narrow spectrum of activity
Gram -ive bacteria: acute and chronic LUTIs
What can the use of Nalidixic Acid result in
Quinolone resistance
Why is Nalidixic acid only indicated for LUTIs
Because it doesn’t achieve sustemic antibacterial levels
MOA of Fluoroquinolones
- Inhibit Topoisomerase II (DNA Gyrase)
- Inhibit Topoisomerase IV
Bactericidal
Inhibition of Topoisomerase II causes
-It prevents the relaxation of +ively supercoiled DNA required for normal transcription and replication
-it also inhibits the cutting and joining action of the enzyme on DNA double helix
Inhibition of Topoisomerase IV causes
-It prevents the removal of supercoils by the enzyme
-it interferes with separation of replicated chromosomal DNA into respective daughter cells during cell division
Resistance Mechanism against Fluoroquinolones
- One or more point mutation in Quinolone binding region of target enzyme
- Change in permeability
How are Fluoroquinolones administered
Orally or IV
Best taken on empty stomach: 1-2hrs before or 2-3hrs after
Adequate fluid must be taken
Absorption of Fluoroquinolones are impaired by what?
by divalent cations (antacids, milk, yogurt)
Causes formation of a chelate
Why is adequate fluid intake needed for Fluoroquinolones?
it will prevent their crystallisation in urine
What should be avoided when taking Quinolones
excessive urine alkalinity becos the drugs would then precipitate in the urine and form crystal urea.
PK of Fluoroquinolones
Metabolized by CYP450 enzyme and some of them actually do inhibit this enzyme (Ciprofloxacin and Levofloxacin to a lower extent)
SEs of Fluroquinolones
GIT disturbances and skin rashes
Seizure risk (exp. Ciprofloxacin)
Hallucinations (rare but in elderly)
Hyperglycaemia in diabteics
Hypoglycameia Type 2 diabetics who are receiving oral hypoglycemic agents
Damage to Growing cartilage and cause arthropathy+arthralgia
Incr. risk of Tendonitis and tendon rupture
Peripheral Neuropathy with incr. time of exposure
Photosensitivity
Rarely aortic aneurysm
SEs of Nalidixic acid
Neurotoxic
Cause Photosensitivity
Could cause seizures
Caution for Nalidixic acid
Elderly as it causes Neurotoxicity
DIS of Fluoroquinolones
Ciprofloxacin+ theophylline
Warfarin+ Ciprofloxacin
NSAIDs: lower seizure threshold= increase. risk of seizures
Oral hypoglycemic agents: gibenclamide
Cipro+Levo may interfere with agents that prolong QT interval
Antacids/minerals
Probencid
Cautions/CIs of Fluroqionolones
Epilepsy (Nalidixic acid CI)
Hepatic failure
Pregnancy/lactation
Babies/children <18yrs
Renal Failure (Nalidixic acid)
Porphyria (Nalidixic acid)
Elderly patients
allergy
G6PD deficiency
Spectrum of Metronidazole
powerful antibacterial action against Anaerobic Organisms
Bactericidal
Antiprotozoal action on trophozoites
Uses of Metronidazole
H.Pylori (PPI+amoxicillin+metronidazole)
Giardiasis: parasitic infection
Acute necrotizing Ulcerative gingivitis
Pseudomembranous colitis
Topical for Rosacea and bacterial vaginosis
MOA of Metronidazole
Undergoes reduction steps to form reactive intermediates
These intermediates then react with DNA like macromolecules and cause:
-Alterations in DNA Helix
-Breaking of DNA chain
Resistance mechanisms against Metronidazole
Decreased uptake
increased removal
decreased activation in bacteria
Altered enzymes that convert active metronidazole to non-toxic derivatives
Admin of Metronidazole
Orally with water=near total ansorp.
Rectal, IV and Topically
PK of Metronidazole
metabolised in liver
10-20 excreted unchanged in urine
SEs of Metronidazole
Nausea, headache, dry mouth
Metallic taste
Mild GIT discomfort
Inhibits alcohol metabolism–> acetaldehyde dehydrogenase inhibited=acetaldehyde accumulates= Disulfiram-like effect
CNS effects
Possible dark colored urine
Additional SEs of Metronidazole in Older patients
Blood counts when used long-term
History of Blood Dyscrasias
DIs of Metronidazole
Cimetidine: M. metabolism decr.
Phenobarbitone: M. metabolism incr.
Phenytoin: M. metabolism decr.
Warfarin: anticoagulant effect incr= incr. risk of bleeding
Alcohol: decreased metabolism
Lithium: plasma levels incr.=toxicity
Disulfiram
CI of Metronidazole
Alcohol use
Caution with Metronidazole
Epilepsy
Porphyria
CNS disease
Impaired hepatic function
1st Trimester of pregnancy (can be used in other trimesters)
Lactation
